Melphalan resistant cells in primary culture had a complement of 40 chromosomes while the sensitive had a mode of 41 chromosomes. Resistant cells required 4 to 5 times the concentration of melphalan in vitro to inhibit growth as did sensitive cells. No difference in melphalan uptake was found at concentrations which blocked the growth of sensitive but not resistant cells. Melphalan resistant cells were also resistant to some but not other selective biochemical inhibitors. These might serve as indicators of the biochemical variation that causes resistance.